The Mechanism Research Of Benazepril In Hepatic Fibrosis Mice And The Effect In The Expression Of Ang?,TGF-?1,IL-1? And INOS

Objective Investigating the effects of benazepril,which is angiotensin inhibitor,on the expression of AngII and TGF-?1,IL-1?and iNOS in liver of hepatic fibrosis mice,and to further explore the mechanism of benazepril to anti-fibrosis of liver.Methods 40 SPF C57BL/6 male mice?weight between 19 g and 22 g?were randomly divided into four group:?1?control group?2?benazepril group?3?CCl₄-induced hepatic fibrosis group.?4?benazepril treatment group,10 in each group.The mice were transported from Jinan Pengyue Experimental Animal Breeding Company to the laboratory rat room for 7 days to adapt the new environment before starting the experiment.The control group did not do any treatment,and was normally reared;the benazepril group was intragastric administration of benazepril?10 mg/kg?every day.CCl₄-induced hepatic fibrosis model group,injected 16%CCl₄ olive oil suspension5mg/kg by intraperitoneal?0.8 ml/kg CCl₄?,once every 3 days.In the benazepril treatment group,except for intraperitoneal injection of CCl₄ every 3 days,benazepril was administered from the beginning of the experiment,at a dose of 10 mg/kg every day.Each group of mice was weighed weekly and adjusted dosages according to the weight of the mice.The experiment is divided into two phases,on the sixth and eighth weekend of the experimengt,five mice from each of the four groups were selected for specimen collection.According to the experiment,the blood samples and liver specimens of the mice were taken.Blood samples were taken for serological detection,and the concentration of alanine aminotransferase?ALT?and aspartate aminotransferase?AST?in mouse serum was detected by automatic biochemical analyzer.In addition,the livers of mice were researched in the following aspects.First,the liver cell cytokine was detected.Secondly,the liver tissue was pathologically examined.The liver was fixed with 4%paraformaldehyde solution and paraffin sectioned,then HE staining and Masson staining,the special staining of the fiber for liver tissue.Results?1?Serological changes:ALT and AST activities were significantly increased in the CCl₄-induced liver fibrosis model group compared with the control group,the levels of ALT were 487.2±78.32U/L,70.40±9.325U/L,P<0.01;the levels of AST were 440.0±58.65U/L,192.0±10.2U/L,P<0.05).The ALT and AST activities of the benazepril-treated mice were significantly lower than those of the model group compared with the model group,the levels of ALT were 92.4±14.65U/L,487.2±78.32U/L,P<0.05;the levels of AST were 268.0±38.78U/L,440.0±58.65U/L,P<0.01).The activities of ALT and AST in the CCl₄-induced liver fibrosis model group were significantly higher than those in the other three groups?P<0.05?.?2?Pathological changes:The structures of liver in control group and benazepril group were normal and intact,the hepatic lobules also had normal structures,without infiltration of inflammatory cells into the liver tissue;the CCl₄-induced liver fibrosis model group were observed a large number of reticular fibrous abnormal proliferation in the portal area,and the fiber spacing is widened,showing the formation of pseudo lobules in the liver of mice.The mice in the benazepril treatment group showed mildly degeneration and necrosis,showing a small amount of fibrosis in the portal area of the liver and a small amount of fiber spacing,which was significantly lighter than model group.?3?ELISA results:AngII expression:CCl₄-induced liver fibrosis model group was higher than control group and benazepril group P<0.01),benazepril treatment group was lower than CCl₄-induced liver fibrosis model group?P<0.05?.?4?qRT-PCR was used to detect the levels of TGF-?1,IL-1?and iNOS,expressed in the liver tissues of each group.The results showed that the expression of these three factors in CCl₄-induced liver fibrosis model group were higher than the three groups?P<0.05?,benazepril treatment group was lower than CCl₄-induced liver fibrosis model group?P<0.05?.Conclusion?1?Benazepril,the angiotensin inhibitors,has a certain effect in anti-fibrotic in CCl₄-induced liver fibrosis mice.?2?In the level of molecular,it is further confirmed that benazepril has the effect of anti-fibrosis,the mechanism may be related to inhibition of the expression of AngII,TGF-?1,IL-1?and iNOS in liver tissues.